The immunosuppression activity of a drug acting as an immunosuppression agent is achieved by inhibiting the growth and differentiation of T-cells. Such immunosuppression agents also have other pharmacological activities like anti-inflammatory and/or antiparasitic, in particular antiprotozoal, like antimalerial activities. The commonly used immunosuppression agents include cyclosporine. There are many cyclosporines known in the art, like cyclosporine A, cyclosporine B, cyclosporine C, cyclosporine D, cyclosporine E etc. The cyclosporine A is preferably used in the clinical field due to its proven pharmacological activity and clinical indication and effectiveness.
This immunosuppression agent, that is, cyclosporine A has been found useful in various other areas, like in auto immune diseases, inflammatory conditions, particularly in inflammatory conditions with an aetiology including an autoimmune component like arthritis.
Further, this immunosuppression agent is applicable in rheumatoid arthritis, arthritis chronica, and progredientic and arthritis deformana. Further, this immunosuppression agent is also applicable in rheumatic diseases.
The immunosuppression therapy using this immunosuppression agent has been proposed or applied in autoimmune hematological disorder, like hemolytic anemia, aplastic anaemia, pure red cell anaemia and idiopathic thrombocytopaenia, systemic lupus erythematosus, dematomyositis, chronic active hepatitis, myasthenia gravis, psoriasis, Steven-Johnson syndrome, idiopathic spure, autoimmune inflammatory bowel disease including ulcerative colitis and crohn's disease, endocrine opthalmopathy, Graves disease, sarcoidosis, multiple sclerosis, primary billiary cirrhosis, juvenile diabetes, like diabetes mellitus Type I, anterior and posterior uveitis, and keratoconjuncativities sicca an vernal keratoconjuncativities, intestinal lung fibrosis, psoriatic arthritis and glomerulonephritis—with or without nephrotic syndrome, like idiopathic nephrotic syndrome or minimal change nephropathy.
Therefore, this immunosuppression agent is widely acceptable immunosuppression agent. This agent is made available in the form of pharmaceutical formulation. The clinical acceptance of such formulations comprising of this immunosuppression agent has suffered due to low solubility and low transport rate and delayed bioavailability and bioabsorption of the immunosuppression agent.
Therefore, in recent past the research has been directed to improve its solubility and transport rate. In addition efforts have been on to improve its early bioavailability, particularly in the upper part of the gastrointestinal tract and bioabsorption.
Various formulations, comprising this immunosuppression agent as one of the essential ingredients, have been developed and made available. Although there are many formulations to form microemulsions, but many of them do not have satisfactorily acceptable bioavailability and bioabsorption. The formation of microemulsions of the clinically acceptable particle size that is of less than 200 mm, particularly of less than 100 nm, is one of the desired requirements for the formulation to be clinically acceptable. Therefore, the efforts are still on to develop new formulations, particularly the formulations which will have better bioavailability, particularly in the upper part of the gastrointestinal tract and better bioabsorption and at the same time will have better solubility and reduced variability, that is inter and intra patient bioabsorption variability, and form the microemulsions of the clinically acceptable particle size.
The another parameter controlling the applicability of formulations of the immunosuppression agent is its manner of administration. The formulation comprising of the immunosuppression agent, particularly of this immunosuppression agent is generally administered after filling it in a soft or hard shell, known as capsule, or in the form of solution for oral administration. The solution form of formulation of the immunosuppression agent is taken after dilution with flavored milk or fruit juice. The mixing with milk or the juice forms the emulsion, particularly microemulsions of varying particle sizes, generally varying above 100 nm, preferably varying above 150 nm. The preferred form of administration of the formulation of this immunosuppression agent is after filling the formulation in a shell, which may be soft or hard shell.
The major problem arises, when the immunosuppression agent or its formulation is administered after filling in a hard or soft-shell. It has been generally observed that, the availability of the immunosuppression agent will depend upon the rupture time of the shell.
The known formulations of the immunosuppression agent, which are made available in the shell, have rupture time of shell varying from 12 minutes to 15 minutes or above. The problem arises due to this longer rupture time, which delays the availability of the immunosuppression agent, which in-turn effects its bioabsorption. The desired rupture time of the shell in order to make the availability of the immunosuppression agent at an early time, preferably in the upper part of the gastrointestinal tract is less than 12 minutes, preferably less than 10 minutes.
Need of Invention
Therefore, there is a need to have a formulation, particularly a selfemulsifiable formulation for oral administration, which can overcome all or some of the disadvantages and limitations of the prior art, as described herein above and more particularly of a selfemulsifiable formulation, which facilitates increased solubility, transport rate, bioavailability and bioabsorption of the immunosuppression agent.